Abstract

Introduction

CD200 is a type I transmembrane glycoprotein that can regulate the activation threshold
of inflammatory immune responses, polarize cytokine production, and maintain immune
homeostasis. We therefore evaluated the functional status of CD200/CD200 receptor
1 (CD200R1) interactions in subjects with systemic lupus erythematosus (SLE).

Methods

Serum CD200 level was detected by ELISA. The expression of CD200/CD200R1 by CD4+ T cells and dendritic cells (DCs) was examined by flow cytometry, and then compared
between SLE patients and healthy controls. Peripheral blood mononuclear cells were
stained with carboxyfluorescein diacetate succinimidyl ester and annexin V/propidium
iodide for evaluation of the effect of CD200 on cell proliferation and apoptosis.
In addition, the effect of CD200 on DC function was determined by transwell migration
assay as well as by measurement of binding and phagocytosis of apoptotic cells.

Results

In SLE patients, the number of CD200+ cells and the level of soluble CD200 were significantly higher than in healthy controls,
whereas the expression of CD200R1 by CD4+ T cells and DCs was decreased. Furthermore, the increased CD200 expression by early
apoptotic cells contributed to their diminished binding and phagocytosis by DCs in
SLE. Importantly, the engagement of CD200 receptor on CD4+ T cells with CD200-Fc fusion protein in vitro reduced the differentiation of T-helper type 17 cells and reversed the defective induction
of CD4+CD25highFoxP3+ T cells by transforming growth factor beta in SLE patients. Conversely, blockade of
CD200-CD200R1 interaction with anti-CD200R1 antibody promoted CD4+ T-cell proliferation.

Conclusion

CD200 and CD200R1 expression and function are abnormal in SLE and may contribute to
the immunologic abnormalities in SLE.